Viral sexually transmitted infections (STIs) are a significant health burden and in particular, women have limited options to protect themselves against them. Herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) are two of the most prevalent viral STIs. Neither of these infections is curable, or preventable with available vaccines. Both have serious sequelae and implications for reproductive health. While HIV and HSV-2 infection have been demonstrated to be highly associated with each other, it has been postulated that infection with each virus may be a risk factor for infection with the other. Although both behavior change and the consistent use of condoms appear to protect against HIV, no prevention strategies for HSV-2 have been demonstrated to be effective. While this lack of effective prevention strategies may in part reflect the inadequacy of studies to date, the biology of HSV-2 -- the fact that viral shedding occurs over a wide anatomic area in the genital region -- suggests that condoms may be less effective for preventing transmission of HSV-2 than for preventing STIs associated with transmission through urethral and cervical secretions. Nonoxynol-9 appears effective in preventing HSV-2 infection in animal models, however, little is known about the effect of nonoxynol-9 in preventing HSV-2 infection in humans. This AIDS-FIRCA proposal is primarily aimed at determining if HSV-2 infection is an independent risk factor for HIV acquisition, and at defining the effect of intravaginal use of nonoxynol-9 in preventing HSV-2 acquisition. This proposal outlines a 3 year prospective cohort study of 1200 HIV uninfected women attending the Spilhaus family planning clinic in Harare, Zimbabwe. Baseline clinical, microbiologic, and laboratory data, including HIV and HSV-2 serologic tests will be obtained. If we establish that infection with HSV-2 increases susceptibility to HIV, and that nonoxynol-9 prevents transmission of HSV-2, we will have revealed a modifiable risk factor for HIV, as well as an inexpensive means of preventing HSV-2 infection and its attendant sequelae. By simply adding an additional tube of blood and a diagnostic test to an established phase III trial in Zimbabwe, the study being proposed here may answer these important questions.